FDA believes that including remote components has notable research benefits, including enabling research into rare diseases and improving access to a representative participant population.
On September 18, 2024, the U.S. Food and Drug Administration (FDA) issued final Guidance on recommendations for conducting decentralized clinical trials (DCTs) for drugs, devices or biological products. Instead of using traditional clinical trial sites, DCTs hold some or all trial activities remotely at locations convenient for trial participants by, for example, using telehealth appointments, outsourcing visits to local healthcare providers, or conducting laboratory tests at outside facilities.
FDA published the DCT Guidance in response to the passage of Section 3606(a) of the Consolidated Appropriations Act, which directed FDA to clarify how to operate DCTs and how such trials can increase trial participant diversity.
Many clinical trials, according to FDA, are already DCTs. FDA believes that including remote components has notable research benefits, including enabling research into rare diseases and improving access to a representative participant population. Importantly though, FDA is clear that DCTs must meet the same regulatory requirements as non-DCTs, though there may be additional considerations when implementing decentralized activities.
The Guidance explains considerations for telehealth as compared to decentralized in-person trial visits and activities. Whether a trial visit is remote or in person, DCTs should indicate in study records the visit date, who conducted the visit and whether it was via telehealth. The study protocol should delineate which visits may be telehealth and which must be in-person visits. Telehealth may be appropriate considering the nature of the investigative product (IP) and trial population’s medical conditions, but telehealth visits should be planned with patient privacy and compliance with governing telehealth laws in mind.
For decentralized in-person activities, trial personnel or local healthcare providers (HCPs) may be sent to homes or alternate locations. FDA is clear that investigators may delegate certain trial activities to local HCPs. Local HCPs who perform trial activities that they are qualified to perform in clinical practice and do not require detailed study knowledge (e.g., knowledge of the protocol or IP) will not be classified as trial personnel. The DCT Guidance clarifies that local HCPs who conduct routine clinical practice are not considered investigators. Investigators are required to explain to local HCPs any specific instructions from the protocol relevant to the activities they perform and conduct regular reviews of data from local HCPs.
Local HCP activities may include measuring vital signs or performing physical examinations. The study protocol should reflect how to manage and respond to adverse events identified remotely. That said, DCTs should include safety monitoring plans that consider how local HCPs can document concerning symptoms and where participants seek local medical assistance.
On the other hand, trained trial personnel must perform activities unique to the study that require knowledge of the protocol. Relatedly, investigators should not delegate obtaining informed consent remotely to local HCPs. FDA explains that only individuals with detailed knowledge of protocol should be tasked with obtaining informed consent. Further, the Guidance instructs that a DCT include in its informed consent process notification of an individual who participants can contact for research related questions and injuries. DCTs should also use a central institutional review board and inform participants of whether local HCPs are involved in the trial, which activities will happen at participant homes, and who will be able to access participant protected health information.
FDA’s Guidance provides risk-based considerations for whether to administer an IP remotely and ship an IP directly to an HCP or participant. FDA advises sponsors to consider an IP’s risk profile when deciding whether to administer outside of a traditional clinical trial site. For example, a local HCP could remotely administer an IP at a participant’s home if the IP is well characterized and does not require specialized monitoring immediately post-administration. IPs in early development stages, however, may need to be administered at a traditional clinical trial site. The Guidance similarly indicates that administration of medical devices outside of traditional clinical sites may be appropriate given low potential serious risk to participants.
Similarly, FDA explains that drugs with good stability profiles may be directly shipped to participants. FDA reminds investigators that they remain responsible for supply supervision in the case of shipment directly to participants or local HCPs. Sponsors should ensure proper corresponding documentation about unused IP disposal, investigator tracking and receipt documentation of IPs, and including instructions for recipients.
The Guidance also clarifies how trial sponsor and investigator activities may be impacted by decentralized activities. Critically, FDA makes clear that sponsor responsibilities are the same in DCTs as in non-DCTs. Sponsors in DCTs should coordinate between and monitor qualifications of contracted services. FDA suggests sponsors keep a data management plan to track data flow. FDA additionally suggests that sponsors include in trial protocol operational details about clinical trial visits, activities separated by trial personnel and local HCPs, IP delivery and safety monitoring.
FDA recommends that sponsors monitor and follow up with data issues and protocol deviations. That said, DCT sponsors should retain a risk-based plan containing a description of how investigation monitoring will occur and ensure data integrity, the frequency of record and source document review, and any components specific to decentralized trial elements.
Broadly, FDA suggests that DCTs limit data variability by introducing protocol for decentralized activities. FDA notes that digital health technologies can be used for remote data transmission for such data and that interested parties should refer to existing Guidance for information on selecting digital health technologies, training and risk management. While it may differ per study to what extent decentralized elements are appropriate, DCTs and trials considering integrating decentralized elements should maintain awareness of the above information and ensure compliance with existing regulatory requirements.
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